Immunotherapy of Cancer and Immunodiagnosis

Immunotherapy of Cancer and Immunodiagnosis Folder Title: ImmunThe Updated: April 26, 2012

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Forms of Cancer Immunotherapy • Non-Specific: Generalized, Non-AntigenSpecific Immune Activation

• Specific: Antigen-specific Response Induced in the Mouse or Patient or Passively Transferred in from Donor Source ImmForm1

Forms of Cancer Immunotherapy Active: Induced Directly in the TumorBearing Animal or in the Patient • Can be Specific or Non Specific

Passive or Adoptive: Immunologically Active Material Transferred into Mouse or Patient as a Passive Recipient • Can be Specific (Antibodies, T-Cells, Antigen-presenting cells – Dendritic Cell Vaccines) • Or Non-Specific (Non-specifically-activated T-Cells; ImmForm2 Cytokines

Active Non-Specific Immunotherapy Bacterial Extracts: Non-Specific Immune Adjuvants • BCG: Bacillus Calmette-Guerin (Attenuated Bovine Tuberculosis Bacterium) • Membrane Extracts of BCG • C Parvum: Corynebacterium parvum (related to diphtheria bacillus) Bacterial Endotoxins: Muramyl Dipeptide Chemical Adjuvants: • Levamisole • Poly IC (Poly-inosinic-Poly-cytidyllic acid) Cytokines: (Can be actively induced or passively transferred) • Interferons • Interleukin 2 (IL2) • Tumor Necrosis Factor (TNF) ActNot

Example of Cytokines in Immunotherpay of Cancer (Passive or Active)

Adoptive Immunotherapy of Cancers (Passive: Donor to Recipient) Non-Specific: • Lymphokine-activated Killer Cells (LAK Cells)\ • Cytokines Specific: Molecular Transfer • Monoclonal Antibodies Specific: Cellular Transfer • Tumor-Infiltrating Lymphocytes (TIL Cells) • Engineered Antigen-Presenting Cells (Dendritic Cells) Adoptive

Some Examples of Active, Specific Immunotherapy (Tumor Vaccines) Unmodified Killed or Attenuated Tumor Cells Unmodified Tumor Antigens Altered Tumor Cells or Tumor Antigens • Lipidized Tumor Antigens • Chemically Derivatized Tumor Antigens • "Xenogenized" Tumor Cells (Virally-infected Cells) • Exposure of Cryptic Antigens Antigenic Peptides from Tumor Antigens

ActSpec

Autologous Tumor Cells Vaccine for Glioblastoma Multiforme April , 2012

50% increase in survival time (48 weeks vs 33 weeks) Minimal side –reactions 40 Patients http://gma.yahoo.com/brain-tumor-vaccine-shows-promiseearly-trial-160209936.html

A phase 2 multicenter trial of about 40 patients with recurrent glioblastoma -- an aggressive brain cancer that typically kills patients within 15 months of diagnosis -- showed that the vaccine safely increased average survival to nearly 48 weeks, compared with about 33 weeks among patients who didn't receive the treatment. The sixmonth survival rate was 93 percent for the vaccinated group, compared with 68 percent for 86 other glioblastoma patients, who were treated with other therapies.

Applications of Monoclonal Antibodies Monoclonal Antibody Diagnosis and TumorImaging • Prostate-specific Antigen (PSA) • Carcino-embryonic Antigen (CEA) • Colon Carcinoma A33 Antigen

Monoclonal Antibody Targeting • Immuno-toxins • Monoclonal antibodies directed to tumor cell surface markers – Can inhibit the cancer cell function – Can target the cancer cell for destruction by the immune response CxMonoAb

Imaging on Metastatic Colon Carcinoma with RadioactiveIodine-Labelled Monoclonal Ab to A33 Ag Lloyd Old, Scientific American, August, 1996, p. 138) SeeMets Arm

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Anti-CD20 Monoclonal Antibodies in Treatment of B-Cell Lymphoma/Leukemia Rituxan#, Zevalin# (Yttrium 90 Radio-isotope Beta-emitter), and Bexxar* (Iodine-131 Radio-isotope Beta and Gamma Emitter) # IDEC Pharmaceuticals. *Corixa and Glaxo Smith Kline)

Anti-CD20

Biotechnology and Clinical Applications of Monoclonals in Cancer Medicine: Leukemia & Lymphoma Therapy Rituxan: IDEC Pharmaceuticals Anti-CD20 Antibody Targeted to B-Cell Lymphoma (Chimeric Mouse CDR's with Human V-Framework and C-regions)

Zevalin: Millennium Pharmaceuticals Anti-CD20 for B-Cell Lymphoma with Radioactive Yttrium; Non-Hodgkin’s Lymphoma

Bexxar:

Anti-CD20 for B-Cell Lymphoma with Radioactive Iodine

Campath: Anti-CD52 for B-Cell Chronic Lymphocytic Leukemia

(See page 141, Immunology, 6th Edition)

MAbLeukemia

Biotechnology and Clinical Applications of Monoclonals in Cancer Medicine: Carcinoma Therapies Herceptin: Genentech Anti-HER2/Neu Growth Factor Receptor in Breast Cancer

Avastin:

Antibody to Vascular-Endothelial Growth Factor Receptor (Anti-angiogenesis Therapy)

Erbitux Antibody to Epidermal Growth Factor Receptor

(See page 141, Immunology, 6th Edition)

MAbCarcinoma

Immunotoxins in Antibody-mediated Cancer Therapy

Class # 26! I made it! I am still here!

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The Endless Mirrors What will remain when our days are done? What will matter when we are gone? That we stalked the crumbled halls of power? Were known by men long lost to time? Famed in some forgotten hour? Or that we wrote a song still sung? Penned a verse that touches souls? Shaped a cure to solace fears To offer hope, to tarry death for childhood’s child in endless years? Birthed a thought that sired ten more? Conceived a dream and passed it on? Forged a link from gone to be, And shined our candle in the endless mirrors That reflect forever down the halls of time. Tom Fondy (See tpfondy.mysite.syr.edu

LLoyd Old, Sci. Amer. Aug, 1996 p. 139

ImmKinds

Please send in your name under “send user data”. Rituxin, Zevalin, Herceptin, Bexxar, Campath, Erbitux, and Avastin are all examples of immunotherapy using _ _ _ _ _ _ _ _ _ _.

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With respect to the use of the Turning Point XR-Transmitter System This response is set at anonymous. You will not be identified with your answer, only that you are responding. 1. 2.

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This is a disaster! Forget about it! This system is not very good. It has a long way to go to be a useful part of Biology courses, but it is worth working on. The XR system is OK. It is worth keeping and using if you can make it work better. The system was actually pretty cool. It made an important contribution to the standards in BIO 501. The use of the XR system was an exciting advance in group communication in the classroom.

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